Total lymphoid irradiation (TLI) is a therapeutic procedure standard in Hodgkin's disease and under active investigation in renal transplantation, multiple sclerosis, rheumatoid arthritis and systemic lupus. The published data indicates that the immunosuppressive effects of TLI involve specific alterations in T lymphocyte numbers and function which must be further defined in order for us to understand the therapeutic and toxic effects of this procedure. This longterm objective will be pursued in a mouse model of TLI, contrasting normal BALB/c with autoimmune NZB/NZW strains. By measuring IL2 activity, IL2 secreting cells, IL2containing cells, and IL2 mRNA we will define the defective IL2 production in TLItreated mice. We will also determine whether TLI interferes with the induction of IL2 receptor expression. It if does, we will define which T cell subpopulation(s) (L3T4+, Lyt2++) are implicated. We will test whether TLI impairs the function of L3T4 T cells, B cells or monocytes in antiDNA production by NZB/NZW mice, whether TLI decreases the proliferative function of L3T4+ cells, whether TLI impairs the function of L3T4+ cells as helpers for the antibody response to Tdependent antigens in BALB/c and NZB/NZW mice, and whether TLI increases the induction of suppressor cells.